The purpose of the proposed study is to establish a real-time alcohol involvement assessment protocol that will make it possible to test the mechanistic pathway of the aldehyde dehydrogenase gene ALDH2. Two technologically advanced devices, a wrist transdermal alcohol sensor (TAS) device and a website that will be accessed by an iPhone, will be further developed and tested as real-time measures of naturalistic drinking. Two methodological advancements will be created in this study to increase the feasibility of this research and of future studies: 1) a computerized program to calculate BACs from TAS data using a limited number of parameters obtained from a laboratory alcohol session, and 2) a website programmed to be flexible and easily modifiable, allowing for additional research questions to be addressed using this technology. These research tools will be used to examine the association of the ALDH2 gene with drinking behaviors. To date, ALDH2 is the gene most strongly associated with alcohol dependence. A mechanistic pathway has been hypothesized for the process by which possession of an ALDH2*2 allele leads to lower rates of alcohol use and problems, but thus far support for this pathway only exists from cross-sectional and laboratory data. The current study proposes to test this hypothesized pathway using ecologically valid assessment of real-time drinking behavior of individuals who possess one ALDH2*2 allele compared with those who possess no ALDH2*2 alleles. Participants will be a subset of 36 Asian American individuals who have participated in a previous study and thus are already well characterized in terms of genotypes, alcohol phenotypes, and other related variables. Each participant will be assessed in a laboratory alcohol challenge to calibrate the TAS device and then will wear the device and use the iPhone and website to record responses to alcohol over the next 2 weeks. The data obtained will be used to show feasibility and to determine effect sizes of ALDH2*2 and the necessary sample size for a larger future study. In addition, substantive hypotheses on the effects of ALDH2*2 will be preliminarily tested in this pilot sample. It is hypothesized that individuals with an ALDH2*2 allele will drink to reach similar subjective levels of response to alcohol compared with those without this protective allele, but will have lower rates of consumption, BACs, and negative consequences. Study feasibility will be assessed using a number of objective (e.g., percent of assessments missed) and subjective (e.g., perceived effects of self- monitoring on behavior) measures. Multilevel models will be used to simultaneously estimate within-person (e.g., BACs, responses to alcohol) and between-person (e.g., ALDH2 genotype) data. These two- and three- level models will compare patterns of use, BACs, subjective responses, and negative consequences across genotypes to determine effect sizes. This study will improve our ability to measure real-time alcohol involvement and our understanding of how genetic variations affect drinking behavior, reactions to alcohol, and the development of alcohol-related problems. PUBLIC HEALTH RELEVANCE: This study will advance methodological techniques for collecting prospective, ecologically valid assessments of real-time drinking behavior. Through the application of these methodological advancements, the proposed research will enhance our understanding of how genetic variations affect drinking behavior, reactions to alcohol, and the development of alcohol-related problems.